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Identification of four new susceptibility loci for testicular germ cell tumour

Author

Listed:
  • Kevin Litchfield

    (The Institute of Cancer Research)

  • Amy Holroyd

    (The Institute of Cancer Research)

  • Amy Lloyd

    (The Institute of Cancer Research)

  • Peter Broderick

    (The Institute of Cancer Research)

  • Jérémie Nsengimana

    (Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology)

  • Rosalind Eeles

    (The Institute of Cancer Research
    Royal Marsden NHS Foundation Trust)

  • Douglas F Easton

    (Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratory)

  • Darshna Dudakia

    (The Institute of Cancer Research)

  • D. Timothy Bishop

    (Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology)

  • Alison Reid

    (Academic Radiotherapy Unit, Institute of Cancer Research)

  • Robert A. Huddart

    (Academic Radiotherapy Unit, Institute of Cancer Research)

  • Tom Grotmol

    (Cancer Registry of Norway)

  • Fredrik Wiklund

    (Karolinska Institutet)

  • Janet Shipley

    (The Institute of Cancer Research)

  • Richard S. Houlston

    (The Institute of Cancer Research)

  • Clare Turnbull

    (The Institute of Cancer Research
    William Harvey Research Institute, Queen Mary University)

Abstract

Genome-wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify additional single-nucleotide polymorphisms (SNPs) associated with TGCT, we conducted a multistage GWAS with a combined data set of >25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P=1.5 × 10−9), 11q14.1 (rs7107174, GAB2, P=9.7 × 10−11), 16p13.13 (rs4561483, GSPT1, P=1.6 × 10−8) and 16q24.2 (rs55637647, ZFPM1, P=3.4 × 10−9). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.

Suggested Citation

  • Kevin Litchfield & Amy Holroyd & Amy Lloyd & Peter Broderick & Jérémie Nsengimana & Rosalind Eeles & Douglas F Easton & Darshna Dudakia & D. Timothy Bishop & Alison Reid & Robert A. Huddart & Tom Grot, 2015. "Identification of four new susceptibility loci for testicular germ cell tumour," Nature Communications, Nature, vol. 6(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9690
    DOI: 10.1038/ncomms9690
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